Manufacturing medical devices by vapor deposition

ABSTRACT

A method of forming a medical device, the method including the steps of providing a substrate, depositing a metallic layer on the substrate by a vapor deposition process, and removing the metallic layer from the substrate. The metallic layer thus removed is the medical device or serves as a basis for forming the medical device. In another aspect, the present invention includes a medical device formed by the process of the present invention.

FIELD OF THE INVENTION

The present invention relates to medical devices and, more particularly,to medical devices having improved mechanical properties that are formedusing vapor deposition techniques.

BACKGROUND OF THE INVENTION

Implantable medical devices such as stents, blood filters, artificialheart valves and the like are typically subjected to hostile workingconditions. For example, stents and blood filters are introduced intothe body while in a compressed shape and are thereafter expanded viaself expansion or mechanical expansion to a final, useful shape whenpositioned to a target location within the body. After deployment, thedevices should have sufficient physical, biological and mechanicalproperties to perform throughout the expected useful lifetime. Moreover,implantable medical devices are typically characterized by complex,intricate shapes and strict dimensional and compositional tolerances.

In view of the stringent requirements of medical devices, the processesused to form these devices must be accurate and reproducible, and obtainthe desired dimensional, compositional and mechanical properties.Conventional production processes, however, are often complex andexpensive. For example, conventional processes used to produce patternedstents often start with wire, tube or sheet materials. Typicalprocessing steps to produce a patterned stent from a wire may includewinding the wire around a mandrel into a complex configuration, weldingthe wire at certain junctions, and heat treating the wire to create thefinal patterned device. To produce a patterned stent from a tube orsheet, conventional processes may include steps such as stamping,cutting or etching a pattern into the starting material, expandingand/or rolling the starting material into a suitable stent shape, andheat treating to create the final device.

Most of the manufacturing steps associated with these conventionalmethods introduce defects into the metallic structure of the formeddevice. The defects can include excessive oxidation, localizeddeformation, surface flaws and the like. These defects often reducedesired properties, such as strength, fatigue resistance and corrosionresistance.

The performance properties of the medical device are not only effectedby manufacturing processes, but are also effected by the materialproperties of the raw material. For instance, if the wire or tube usedto form a medical device contains material or structural defects, theformed medical device may also often contain similar or greater defects.Some defects in the formed device may be reduced by techniques, such asannealing, but these techniques often impart other undesirable effects.For instance, annealing often requires high temperature treatment of ametallic device to recrystallize its microstructure to reduce grain sizeand residual stress. Such a high temperature treatment can often impartphysical deformation of the device due to thermal heating and coolingsteps or due to the change in the microstructure itself. Because medicaldevices often require intricate shapes and strict dimensionaltolerances, physical deformation of the device during manufacturing isoften a problem.

Furthermore, the compositional properties of the raw material used toform the medical device also effects the final properties of the device.Impurities often degrade useful mechanical properties, reduce corrosionresistance and effect the biocompatability of the medical device.

Accordingly, a need exists for a manufacturing process to form a medicaldevice without the disadvantages of the prior art. Furthermore, a needexists for a medical device with improved biocompatability andmechanical properties.

In view of the shortcomings of conventional medical device manufacturingprocesses, there exists a need for a process that facilitates thereproducible production of medical devices having improved mechanicalproperties.

SUMMARY OF THE INVENTION

In one aspect, the present invention provides a method of forming amedical device, the method including the steps of providing a source ofbiocompatible metal; providing a substrate; depositing a biocompatiblemetallic layer on the substrate from the source by a vapor depositionprocess; and removing the metallic layer from the substrate. Themetallic layer thus removed is the medical device or serves as a basisfor forming the medical device.

In another aspect, the present invention includes a medical deviceformed by the process of the present invention. The medical devices haveat least one or more members formed from biocompatible metals.

The medical devices also have a crystallographic structure that isproduced by the vapor deposition methods of the present invention.Desirable crystallographic structures include amorphous, nanocrystallineand monocrystalline structures. Furthermore, the medical devices mayinclude monoisotopic metal or alloys of monoisotopic metals.

BRIEF DESCRIPTION ON THE DRAWINGS

FIG. 1 shows a schematic of a method for forming a medical deviceaccording to a vapor deposition method of the present invention.

FIG. 2 shows a medical device formed according to a vapor depositionmethod of the present invention.

FIG. 3 shows a second medical device formed according to a vapordeposition method of the present invention.

FIG. 4A shows an example of a vapor deposition apparatus in accordancewith an embodiment of the present invention.

FIG. 4B shows the vapor deposition apparatus of FIG. 4A with massanalysis ans separation in accordance with an embodiment of the presentinvention.

FIG. 5 shows a substrate having a deposition layer, in accordance withan embodiment of the present invention.

FIG. 6A depicts a cross sectional view of the substrate with adeposition layer of FIG. 5 taken along the 6-6 axis.

FIG. 6B shows a multi-layered substrate, in accordance with anotherembodiment of the present invention.

FIG. 7 shows the cross sectional view of deposition layer of FIG. 6after removal of the substrate.

FIG. 8 shows a multi-layered substrate having a release layer, inaccordance with another embodiment of the present invention.

FIGS. 9 and 10 show side and end views, respectively, of an example of adeposition mask used in accordance with an embodiment of the presentinvention.

FIG. 11 shows a portion of a patterned substrate having a vapordeposited metallic layer, in accordance with an embodiment of thepresent invention.

FIG. 12 shows a portion of a second patterned substrate having a vapordeposited metallic layer, in accordance with an embodiment of thepresent invention.

FIG. 13 shows a portion of the patterned substrate of FIG. 11 afterremoval of a portion of the metallic layer.

FIG. 14 shows a stent wire for use in forming the medical device of FIG.3, in accordance to an embodiment of the present invention.

FIG. 15 shows an example of a vapor deposition apparatus for forming thestent wire of FIG. 14, in accordance with an embodiment of the presentinvention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention overcomes many of the difficulties associated withconventional medical devices and the methods used to form such medicaldevices. By using vapor deposition techniques for the formation ofmedical devices, the composition, thickness, surface roughness, andmicrostructure of devices formed in accordance with the presentinvention are accurately and precisely controlled. The medical devicesformed by the process of the present invention are tailored to havedesired compositions, mechanical properties, and geometries.

In one aspect as illustrated in FIG. 1, the present invention isdirected to a method of forming a medical device, the method includingthe steps of providing a substrate and source material, depositing ametallic layer of source material on the substrate by a vapor depositionprocess, and removing the metallic layer of source material from thesubstrate.

At step 10, a substrate is provided to serve as a target for sourcematerial by vapor deposition. As described further herein, the materialof the substrate and the configuration of the substrate are selectedaccording to the desired aspects of the medical device or medical memberformed by the process of the present invention.

At step 12, a source material for vapor deposition is provided.Desirably, the source material is biocompatible material, as describedfurther herein, suitable for use as a medical device.

At step 14, source material is deposited as a metallic layer at thetarget or onto the substrate by a vapor deposition process.

At step 16, the metallic layer from the substrate is removed. Themetallic layer thus removed is the medical device or serves as a basisfor forming the medical device. In another aspect, the present inventionincludes medical devices made by the process of the present invention.

“Vapor deposition,” as used herein, refers to any process of depositingmetals and metal compounds from a source to a substrate or target bydissipating metal ions from the source in a vaporous medium. Examples ofuseful vapor deposition processes for use in the present inventioninclude physical vapor deposition processes such as evaporation, andsputtering. Direct and assisted ion beam deposition, and chemical vapordeposition are also useful. These useful vapor deposition processes aregenerally described below.

In the evaporation process, vapor is generated by heating (e.g., byelectron beam interaction) a source material to a temperature to causethe vaporization thereof. The evaporating metal atom leaves the surfaceof the source material in a straight line. Therefore, highest qualitydeposition layers are deposited when the source-to-substrate distance isless than the mean path distance between collisions of the vaporizedmetal and the surrounding vacuum chamber. At chamber pressures greaterthan 10⁻¹ Pa, a useful source-to-substrate distance is generally lessthan 500 mm. At 10⁻² Pa, this distance can be increased to over 4000 mm.Furthermore, it is useful to rotate or translate the substrate withinthe suitable source-to-substrate distance to ensure that the entiresurface of the substrate is coated. Deposition rates using commerciallyavailable equipment typically exceed 0.05 mm per minute.

In the sputtering process, a source is bombarded with ions of an inertgas to cause the dislodgment of material therefrom. The source of ionsis typically an ion beam or plasma discharge. In this technique, asource material is placed in a vacuum chamber with a substrate material.The chamber is evacuated to 10⁻³-10⁻⁵ Pa, and backfilled with an inertgas such as argon to a pressure of 0.1-10 Pa to sustain a plasmadischarge. The substrate is made positive, relative to the sourcematerial, by a radio-frequency power source. When the applied potentialreaches the ionization energy of the gas, electrons, generated at thecathode, collide with the gas atoms, ionizing them and creating aplasma. These positively charged ions, having high kinetic energy, areaccelerated toward the cathode source material, thus dislodging atomsthat then travel across the electrode gap. These dislodged atoms arethen deposited onto the substrate. Because of the energy of these atoms,their adherence to the substrate is generally better than if they weredeposited by vacuum evaporation.

Ion beam assisted deposition (IBAD) utilizes a high energy beam of heavyions to help densify the deposited metals, such as metals deposited bysputtering or evaporation processes. A useful ion beam assisteddeposition method further includes mass analysis of the ion beam beforethe ionized source material is deposited onto the substrate. This methodaccelerates the ion beam and passes it through a filter typicallycontaining magnetic and/or electrostatic fields to separate differentmass-weight species. This filter is often referred to as an ExB filterand is commercially available. Those of skill in the art can select anExB filter with desirable features to be useful with the presentinvention. A particular mass-weight species is then targeted at thesubstrate. When the ion sources are individual pure element ingots, thistechnique can be used to separate the isotopes of an element and todirect a particular isotope to the substrate. Because naturallyoccurring elements typically consist of a range of atomic weights orisotopes (See Table 1 below), this method is useful in selecting aparticular isotope for forming a medical device. For instance, titaniumwith atomic weight of 48 may be selected for vapor deposition whilerejecting titanium with atomic weights of 46, 47, 49 and 50.Furthermore, other impurities, such as oxygen, that may be contained inthe elemental ingot may be filtered away from the substrate with thismethod. TABLE 1 Naturally Occurring Isotopes of Ti &Ni Atomic AtomicNatured Element No. Weight Occurrence % Titanium 22 46 7.9(₂₂Ti^(47.96)) 47 7.3 48 73.9 49 5.5 50 5.4 Nickel 28 58 67.8(₂₈Ni^(58.7)) 60 26.2 61 1.2 62 3.7 64 1.1

The removal of impurities and the filtering of particular isotopes areuseful in the present invention. The crystalline structure of themetallic medical article may be affected by impurities. Single crystalor monocrystalline materials are more easily formed when levels ofimpurities are minimized. Furthermore, medical devices formed as amonocrystalline, monoisotopic material are useful with the presentinvention.

Large, single crystals of metals can be grown by a number of methods.One simple method is to melt the metal in a conical vessel, and thenlower the vessel slowly from the furnace, point first. Under controlledtemperature conditions a single seed forms at the point of the cone andcontinues to grow until it fills the cone or unit crystal growth isotherwise terminated. The single crystal may also slowly be drawn fromthe vessel as to make a filament of a single crystal. Impurities in thevessel often terminate single crystal growth. Nevertheless, a singlecrystal filament or write may suitable be formed. The present invention,however, is not limited to “melting” techniques for forming singlecrystals and other methods may suitable be used.

Such a single crystal filament or wire may then be used as a substratein a vapor deposition process. Ionized metal atoms deposit on thissubstrate and may form the same crystalline structure, i.e.,monocrystalline structure, as contained in the substrate. Ion beamdeposition with mass analysis is a useful vapor deposition process toform monocrystalline medical devices because impurities and mass-speciescan be controlled. In such a manner a monoisotopic, monocrystallinemedical article, such as a stent or a stent wire, may suitably beformed.

Another useful method of the present invention for forming medicaldevices is crystallization of structures formed with an amorphousmorphology. An amorphous metallic structure may be deposited onto asubstrate by vapor deposition when the substrate is a dissimilarmaterial from the deposited material. The amorphous structure maysubsequently be treated or aged under conditions that are well belowtypical annealing temperatures, such as about or near room temperature,to form a monocrystalline metallic structure. Ion beam deposition methodis useful because impurity levels can be substantially reduced ascompared to other methods. Reduced impurity levels facilitate the growthof single crystals. Moreover, monocrystalline and monoisotropic crystalscan be suitably formed by vapor deposition methods, especially by ionbeam depositions with mass analysis.

Furthermore, as compared to conventional processes, enhanced mechanicalproperties for medical devices can be obtained by minimizing the grainsize of the metallic structure. Conventional grain sizes are on theorder of ten microns or larger. A medical device with a nanocrystallinestructure is useful because of its enhanced mechanical properties, forinstance fatigue resistance and corrosion resistance. A nanocrystallinestructure in a biocompatible material with a grain size ranging fromabout 1 to 500 nanometers is useful as a medical device. Also useful isa biocompatible material with a grain size of about 1 to 100 nanometers.Furthermore, a nanocrystalline structure in a biocompatible materialwith a grain size of about 1 to 50 nanometers is useful as a medicaldevice. Moreover, a biocompatible material with a grain size of about 1to 10 nanometers is also useful as a medical.

Such nanocrystalline structures can be formed by depositing an amorphouslayer of desired material onto a substrate or target. Theabove-described aging techniques can be used to form nanometer sizedcrystals. Furthermore, the orientation of the nanometer sized grains canbe controlled to yield a orderly grain structure with substantiallysimilar crystal orientation. A useful method for forming such structuresis through epitaxy where desired material is deposited onto a substratehaving a crystalline structure, such as an orientated, nanocrystallinestructure, and the deposited material forms a crystalline structuresimilar to that of the substrate.

The present invention is described with reference to the formation of ametallic stent, although it should be understood that the process of thepresent invention can be used to form any applicable medical device suchas, for example, blood filters and artificial heart valves. Furthermore,the medical devices of the present invention have at least one or moremetallic members. These members have discrete dimensions and shapes asdesired for particular medical devices and for particular medicalapplications.

Various stent types and stent constructions may be employed in theinvention. Examples of the various stents include, without limitation,self-expanding stents and balloon expandable stents. The stents may becapable of radially contracting, as well, and in this sense can be bestdescribed as radially or circumferentially distensible or deformable.Self expanding stents include those that have a spring-like action whichcauses the stent to radially expand, or stents which expand due to thememory properties of the stent material for a particular configurationat a certain temperature. Nitinol is one material which has the abilityto perform well while both in spring-like mode, as well as in a memorymode based on temperature. Other materials are of course contemplated,such as stainless steel, platinum, gold, titanium and otherbiocompatible metals.

The configuration of the stent may also be chosen from a host ofgeometries. For example, wire stents can be fastened into a continuoushelical pattern, with or without a wave-like or zig-zag in the wire, toform a radially deformable stent. Individual rings or circular memberscan be linked together such as by struts, sutures, welding orinterlacing or locking of the rings to form a tubular stent. Tubularslotted stents are also useful in the present invention.

In one aspect of the present invention, a metallic stent, such as aslotted metallic stent 100 as depicted in FIG. 2 or a wire-framedmetallic stent 200 as depicted in FIG. 3, is formed according to anembodiment of the present invention. As depicted in FIG. 4A, a mandrel105 is placed a vacuum chamber 110 or other suitable device for vapordeposition processes. The mandrel 105 is, for example, a metallic wireor any other suitable cylindrical element.

The mandrel 105 is desirably mounted onto a motor driven rotary mount106 to assist in the production of a uniform deposition. Duringdeposition, the rotary mount 106 rotates, as depicted by vector A, at aspeed determined by the medical device equipment and process parameters,for instance about 1-60 rev/min. After forming an appropriate vacuumpressure in the chamber 110, the vapor deposition process commenceswhereby a metallic layer 115 is deposited onto the mandrel 105 as shownin FIG. 5. The source of the material deposited as the metallic layer115 is source material 120 that is placed the vacuum chamber 110. Thevapor deposition process continues until the metallic layer 115 achievesa desired thickness. As described by the aforementioned vapor depositiontechniques, metallic laser 115 can be formed to have a range ofcrystalline morphologies, including a monocrystalline or ananocrystalline morphology.

Metallic layer 115 may also be formed as having a monoisotopicmorphology through use of mass analysis of an ion beam before theionized source material is deposited as metallic layer 115. As depictedin FIG. 4B, vacuum chamber 110 may further include filter 180 andtemplates 181 and 182, interrelated as shown. Filter 180 may be used toseparate the isotopes of an element or contaminants that may be presentin source material 120. Desirable filter 180 is a filter containingmagnetic and/or electrostatic fields, such as an ExB filter. Templates181 and 182 are useful for targeting a particular isotope toward mandrel105 while preventing other isotopes or contaminants from reachingmandrel 105. For example, as depicted in FIG. 4B, beam 190 contains aparticular isotope of source material 120 to be deposited on mandrel105. Other beams, such as beams 191 A-D, contain other isotopes orcontaminants of source material 120 and these other beams are preventedfrom reaching mandrel 105 through use of templates 181 and 182.

Following deposition, the coated mandrel 105 is removed from the chamber110. The top and bottom ends 107, 108 of the coated mandrel 105 areremoved by any suitable means such as, for example, cutting with alow-speed cutting saw equipped with a diamond-impregnated copper cuttingwheel. Alternatively, multiple cuts can be made of a relatively longcoated mandrel to yield numerous coated mandrel portions, each of whichis used to form a stent.

As depicted in FIG. 6A, which is a cross sectional view of the coatedmandrel 105 taken along the 6-6 axis, the metallic layer 115 encompassesmandrel 105. To form a medical device or a member of a medical devicethe metallic layer 115 is removed from mandrel 105. The metallic layer115 is removed from the coated mandrel 105 by any suitable techniquesuch as, for example, exposing the coated mandrel 105 to a solutionwhich will dissolve the mandrel material but not the metallic layer 115.As an example, when the mandrel 105 is a low carbon steel wire and themetallic layer 115 comprises nitinol, the mandrel 105 may be dissolvedwith a suitable acid, such as hydrochloric acid, which does not destroythe metallic layer 115 to form a medical device or member. FIG. 7depicts a view of the metallic layer 115 of FIG. 6A after the mandrel105 has been removed.

As an alternative, the metallic layer 115 may be removed from themandrel 105 by machining techniques such as, for example, drilling,grinding, milling, laser cutting, laser milling and the like.

As another alternative, a release layer 130 is formed between themandrel 105 and the metallic layer 115 as shown in FIG. 8. The releaselayer 130 is applied to the mandrel 105 by any suitable coatingtechnique such as, for example, dipping, spraying, rolling,electroplating, vapor deposition and the like. After deposition of themetallic layer II 5, the release layer 130 is removed by machining or,desirably, by dissolving it in a solution that attacks the material ofthe release layer 130 while not affecting the materials of the mandrel105 and the metallic layer 115. For instance, sulfuric acid is a usefulrelease agent when the mandrel is titanium or tantalum, the releaselayer is copper and the metallic layer is nitinol.

After release from the mandrel 105 or from the release layer 130, themetallic layer 115 either serves as a stent or as the basis for forminga stent by further processing. Desirably, a stent formed in accordancewith the present invention will have a pattern of openings, such asopenings 101 in slotted metallic stent, therein to help facilitateexpansion for deployment within a body lumen. In one aspect, theopenings 101 in the stent 100 are formed by machining such openings intothe metallic layer 115 after removal from the mandrel 105.

In another aspect, a mask 150 is used to surround the mandrel 105 duringdeposition of the metallic layer 115. FIGS. 9 and 10 show side and endviews, respectively, of an example of the mask 150. The mask 150 isshaped as the inverse of the intended final stent configuration suchthat the vapor deposition process results in a pattern of openings, suchas openings 101 in slotted metallic stent 100, in the metallic layer 15.A mask may also be suitably used to form other shapes or configurations,such as openings 210 in wire-formed metallic stent 200.

In yet another aspect, the mandrel 105, as illustrated in FIG. 11, ispatterned to cause a corresponding pattern to be formed in the depositedmetallic layer 1115. FIG. 11 is a partial longitudinal view of coatedmandrel 105 of FIG. 5 taken along the 11-11 axis. The pattern in themandrel 105 may be, for example, a negative pattern 160 in which theintended pattern for stent 100 is recessed into the mandrel 105.Alternatively, the pattern in the mandrel 105 may be a positive pattern170, as depicted in FIG. 12, in which the intended pattern for stent 100is extended from the mandrel 105. Negative patterns, positive patternsor combinations thereof may be used with the present invention. Asdepicted in FIG. 13, portions of the metallic layer 115 not intended tobe part of the stent 100 is removed by any suitable process such as, forexample, machining, etching, laser cutting and the like to form amedical device or a member of a medical device. The remaining portionsof the metallic layer 115 in FIG. 13 may be removed from the mandrel 105by use of the aforementioned methods of the present invention.

The positive and negative patterns on the mandrel are configured toproduce a reverse image of the stent on the surface of the mandrel.Machinery for producing the reverse image on the surface of the mandrelmay vary depending on the complexity of the geometric pattern, type ofmaterial used for the mandrel and other considerations. Fine cuttingheads or tools may be used to machine a pattern into the mandrel withmicro-machining methods. Etching, molding and lase ring techniques arealso useful methods for forming the reverse image on the mandrel.

The reverse image which is formed on the surface of the mandrel isdesirably free or substantially free from micropores or defects becausethe quality of the subsequently vapor deposited stent may depend, inpart, on the surface quality. Thus, subsequent to the mechanicalformation of the reverse image, chemical etching or other polishingtechniques may be used to remove surface imperfections. Additionally,oils, oxides and other matter which may interfere with the quality ofthe vapor-deposited metallic layer are removed prior to the vapordeposition. Chemical and electrochemical cleaning may be used to socondition the surface of the micro-machined mandrel.

In another aspect of the present invention, a fine metal wire may beused as the target for vapor deposition. As depicted in FIGS. 14 and 15,metallic layer 215 is deposited onto wire 205 with vapor depositionmethods of the present invention to form stent wire 225. Wire 205 isintroduced into vacuum chamber 210 through seal 231. Source material 20is deposited by vapor deposition onto wire 205. The coated wire 205exits vacuum chamber 210 through seal 232 seals 231 and 232 serve tomaintain vacuum conditions within vacuum chamber 210 as wire 205 ispassed through vacuum chamber 210.

As depicted in FIG. 15, wire 205 can be cycled through vacuum chamber210 through multiple passes until a desire thickness of metallic layer215 is obtained. After achieving the desired thickness of metallic layer215, stent wire 225 may removed from the vapor deposition process toform wire-formed metallic stent 200, or other medical device. Stent wire225 can be formed into stent 200 by appropriate bending and attaching,such as welding, techniques.

Metallic layer 215 can be fabricated as a single crystal material,monocrystalline and monoisotopic material or a nanocrystalline materialby previously described inventive methods. Desirably, stent wire 225 hasa single crystal structure.

The material deposited as the metallic layer 115 or 215 is any suitablematerial for use in medical device applications such as, for example,nitinol, stainless steel, titanium, cobalt-chromium alloys, gold,platinum, niobium, zirconium, silver, tantalum and alloys thereof. Thevapor deposition of these materials results in a deposited metalliclayer 115 having a fine, equiaxed microstructure which may be preciselyestablished as a function of process parameters. These microstructuresin turn affect mechanical properties such as strength and corrosionresistance.

The process of the present invention is further amenable to thedeposition of multiple layers for the further improvement of desiredmedical device properties. For example, as depicted in FIG. 6B, thedeposited metallic layer 115 is optionally coated with a layer 116 of aradiopaque material such as platinum or tantalum to impart radiopacityto the medical device. The deposited metallic layer 115 is alsooptionally coated with a layer 117 of a material, such as carbon, toimpart thrombogenicity and corrosion and/or fatigue resistance to themedical device. If applied to the metallic layer 115, such additionalcoatings 116, 117 are applied singularly or in any combination.Moreover, the additional coatings 116, 117 are desirably applied in thesame vacuum chamber 110 used for the deposition of metallic layer 115.To facilitate the deposition of the additional coatings 116, 117, it ispreferred that the chamber 110 be equipped to receive and depositmultiple sources so that the additional coatings 116, 117 can bedeposited immediately following the deposition of metallic layer 115without breaking vacuum. Alternatively, the source materials for theadditional coatings 116, 117 may be sequentially loaded into the chamber110 for deposition.

Following the deposition of the metallic layer 115 and optional layers116, 117, the coated mandrel 105 is removed from the chamber 105. Thelayers 115, 116, 117 are optionally subjected to further processingsteps such as, for example, machining, heat treating, oxidizing,welding, attaching to other components, applying organic coatings, andthe like. If the layer 115 comprises nitinol or another shape memoryalloy, it is subjected to thermomechanical “training” steps to inducethe shape memory effect, as is known in the art.

The present invention is further described with reference to thefollowing non-limiting examples.

EXAMPLES Example 1

A patterned nitinol stent is formed according to the followingprocessing steps. A steel wire mandrel measuring about 10 mm in diameterand 30 mm in length is placed in a vacuum chamber on a motor drivenrotary mount. Also mounted in the chamber is a nitinol source targetcomprising about 55.9 wt % nickel and the balance essentially titanium.The chamber is then evacuated to a pressure of less than 10⁻⁶ torr.Argon is introduced into the chamber at a flow rate of 100 cm³/min,producing an operating pressure of about 10 millitorr. A plasma is thengenerated in the chamber by ion bombardment of the nitinol target,resulting in nitinol deposition onto the wire mandrel. Sputterdeposition is continued until the thickness of the deposited nitinollayer is about 0.25 mm, after which the coated mandrel is removed fromthe chamber.

The coated mandrel is cut at both ends to a length of about 20 mm. Apattern is formed in the coated mandrel by machining oval-shaped holesthrough the thickness thereof. The deposited nitinol layer is removedfrom the mandrel by dissolving the mandrel in hydrochloric acid thusyielding a functional nitinol stent with a fine, equiaxed andnanocrystalline microstructure. The grain size of the nanocrystallinestructure can be measured by a number of suitable techniques. A usefultechnique includes transmission electron microscopy to measure grainsizes at multiple grain boundaries with computer averaging of themeasured results. A grain size of the nanocrystalline structure ismeasured to be less than 10 nanometers by this technique.

Example 2

A patterned nitinol stent is formed according to the followingprocessing steps. A steel wire mandrel measuring about 10 mm in diameterand 30 mm in length is placed in a vacuum chamber on a motor drivenrotary mount. The mandrel is machined prior to deposition to reflect thedesired stent pattern. Specifically, the mandrel is machined to includeslots measuring about 2 mm in length and 1 mm in width. Also mounted inthe chamber is a nitinol source target comprising about 55.9 wt % nickeland the balance essentially titanium. The chamber is then evacuated to apressure of less than 10⁻⁶ torr. Argon is introduced into the chamber ata flow rate of 100 cm³/min, producing an operating pressure of about 10millitorr. A plasma is then generated in the chamber by ion bombardmentof the nitinol target, resulting in nitinol deposition onto the wiremandrel. Sputter deposition is continued until the thickness of thedeposited nitinol layer is about 0.25 mm, after which the coated mandrelis removed from the chamber. After deposition, the deposited nitinollayer is patterned due to the pattern of the underlying mandrel.

The coated mandrel is cut at both ends to a length of about 20 mm. Thedeposited nitinol layer is removed from the mandrel by dissolving themandrel in hydrochloric acid. After dissolving the mandrel, the interiorof the stent is machined by laser milling to remove residual nitinolthat had been deposited on the mandrel walls that defined the slots. Theresult is a patterned nitinol stent with a fine, equiaxednanocrystalline microstructure. The grain size of the nanocrystallinestructure is measured to be less than 10 nanometers by transmissionelectron microscopy with computer averaging.

Example 3

A patterned nitinol stent is formed according to the followingprocessing steps. A steel wire mandrel measuring about 10 mm in diameterand 30 mm in length is placed in a vacuum chamber on a motor drivenrotary mount. A cylindrical mask is used to surround the mandrel duringdeposition to form a pattern in the deposited nitinol layer. The mask isconfigured so as to result in the deposition layer with oval-shapedopenings therein, the openings measuring about 2 mm in length and 1 mmin width. Also mounted in the chamber is a nitinol source targetcomprising about 55.9 wt % nickel and the balance essentially titanium.The chamber is then evacuated to a pressure of less than 10⁻⁶ torr.Argon is introduced into the chamber at a flow rate of 100 cm³/min,producing an operating pressure of about 10 millitorr. A plasma is thengenerated in the chamber by ion bombardment of the nitinol target,resulting in nitinol deposition onto the wire mandrel. Sputterdeposition is continued until the thickness of the deposited nitinollayer was about 0.25 mm, after which the coated mandrel is removed fromthe chamber.

The coated mandrel is cut at both ends to a length of about 20 mm. Thedeposited nitinol layer is removed from the mandrel by dissolving themandrel in hydrochloric acid thus yielding a patterned nitinol stentwith a fine, equiaxed nanocrystalline microstructure. The grain size ofthe nanocrystalline structure is measured to be less than 10 nanometersby transmission electron microscopy with computer averaging.

Example 4

A patterned nitinol stent is formed according to the followingprocessing steps. A steel wire mandrel measuring about 10 mm in diameterand 30 mm in length is placed in a vacuum chamber on a motor drivenrotary mount. Also mounted in the chamber are the following sourcematerials: a nitinol source target comprising about 55.9 wt % nickel andthe balance essentially titanium; and a platinum source target. Thechamber is then evacuated to a pressure of less than 10⁻⁶ torr. Argon isintroduced into the chamber at a flow rate of 100 cm³/min, producing anoperating pressure of about 10 millitorr. A plasma is then generated inthe chamber by ion bombardment of the nitinol target, resulting innitinol deposition onto the wire mandrel. Sputter deposition iscontinued until the thickness of the deposited nitinol layer is about0.25 mm, after which the platinum is sputter deposited to a thickness ofabout 0.1 mm. The coated mandrel is then removed from the chamber.

The coated mandrel is cut at both ends to a length of about 20 mm. Apattern is formed in the coated mandrel by machining oval-shaped holesthrough the thickness thereof. The deposited nitinol layer is removedfrom the mandrel by dissolving the mandrel in hydrochloric acid thusyielding a patterned nitinol stent with a fine, equiaxed nanocrystallinemicrostructure and a radiopaque platinum coating. The grain size of thenanocrystalline structure is measured to be less than 10 nanometers bytransmission electron microscopy with computer averaging.

Example 5

A patterned nitinol stent is formed according to the followingprocessing steps. A steel wire mandrel measuring about 10 mm in diameterand 30 min in length is placed in a vacuum chamber on a motor drivenrotary mount. Also mounted in the chamber are the following sourcematerials: a nitinol target comprising about 55.9 wt % nickel and thebalance essentially titanium; a platinum source target; and a carbonsource target. The chamber is then evacuated to a pressure of less than10⁻⁶ torr. Argon is introduced into the chamber at a flow rate of 100cm³/min, producing an operating pressure of about 10 millitorr. A plasmais then generated in the chamber by ion bombardment of the nitinoltarget, resulting in nitinol deposition onto the wire mandrel. Sputterdeposition is continued until the thickness of the deposited nitinollayer is about 0.25 mm, after which the platinum is sputter deposited toa thickness of about 0.1 mm. Following platinum deposition, the carbonsource is evaporated by electron beam interaction. The coated mandrel isthen removed from the chamber.

The coated mandrel is cut at both ends to a length of about 20 mm. Apattern is formed in the coated mandrel by machining oval-shaped holesthrough the thickness thereof. The deposited nitinol layer is removedfrom the mandrel by dissolving the mandrel in hydrochloric acid thusyielding a patterned nitinol stent with a fine, equiaxed nanocrystallinemicrostructure and a radiopaque platinum coating. The grain size of thenanocrystalline structure is measured to be less than 10 nanometers bytransmission electron microscopy with computer averaging.

In the foregoing the invention has been described by means of specificembodiments, but it will be understood that various changes andmodifications may be performed without deviating from the scope andspirit of the invention.

1-23. (canceled)
 24. An implantable medical device, comprising one ormore biocompatible metallic members, said one or more members having amonocrystalline, monoisotopic morphology.
 25. The device of claim 24,wherein said one or more members is selected from the group ofbiocompatible metals consisting of nitinol, platinum, titanium, nickel,gold, niobium, zirconium, silver, tantalum, cobalt, chromium, stainlesssteel, and alloys thereof.
 26. The device of claim 24, wherein said oneor more members is an alloy of monoisotopic biocompatible metals, saidmetals selected from the group consisting of nitinol, platinum,titanium, nickel, gold, niobium, zirconium, silver, tantalum, cobalt,chromium, stainless steel, and alloys thereof.
 27. The device of claim24, wherein said device is a stent.
 28. The device of claim 24, whereinsaid device is a blood filter.
 29. The device of claim 24, wherein saiddevice is an artificial heart valve.
 30. An implantable medical devicecomprising one or more biocompatible metallic members having ananocrystalline morphology.
 31. The device of claim 30 wherein saidnanocrystalline morphology is defined by grain sizes from about 1 toabout 500 nanometers.
 32. The device of claim 30, wherein saidnanocrystalline morphology is defined by grain sizes from about 1 toabout 50 nanometers.
 33. The device of claim 30, wherein said one ormore members is further defined by a monoisotropic morphology.
 34. Thedevice of claim 30, wherein said one or more members is selected fromthe group of biocompatible metals consisting of nitinol, platinum,titanium, nickel, gold, niobium, zirconium, silver, tantalum, cobalt,chromium, stainless steel, and alloys thereof.
 35. The device of claim30, wherein said one or more members is an alloy of monoisotopicbiocompatible metals, said metals selected from the group consisting ofnitinol, platinum, titanium, nickel, gold, niobium, zirconium, silver,tantalum, cobalt, chromium, stainless steel, and alloys thereof.
 36. Thedevice of claim 30, wherein said device is a stent.
 37. The device ofclaim 30, wherein said device is a blood filter.
 38. The device of claim30 wherein said device is an artificial heart valve.